Title: | Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia |
Authors: | Cho, Kazutoshi Browse this author →KAKEN DB |
Yamada, Masafumi Browse this author |
Agematsu, Kazunaga Browse this author |
Kanegane, Hirokazu Browse this author |
Miyake, Noriko Browse this author |
Ueki, Masahiro Browse this author |
Akimoto, Takuma Browse this author |
Kobayashi, Norimoto Browse this author |
Ikemoto, Satoru Browse this author |
Tanino, Mishie Browse this author →KAKEN DB |
Fujita, Atsushi Browse this author |
Hayasaka, Itaru Browse this author |
Miyamoto, Satoshi Browse this author |
Tanaka-Kubota, Mari Browse this author |
Nakata, Koh Browse this author |
Shiina, Masaaki Browse this author |
Ogata, Kazuhiro Browse this author |
Minakami, Hisanori Browse this author →KAKEN DB |
Matsumoto, Naomichi Browse this author |
Ariga, Tadashi Browse this author →KAKEN DB |
Keywords: | 2',5'-oligoadenylate synthetase 1 |
OAS1 |
pulmonary alveolar proteinosis |
PAP |
hypogammaglobulinemia |
alveolar macrophage |
Issue Date: | 1-Mar-2018 |
Publisher: | Cell Press |
Journal Title: | The American Journal of Human Genetics |
Volume: | 102 |
Issue: | 3 |
Start Page: | 480 |
End Page: | 486 |
Publisher DOI: | 10.1016/j.ajhg.2018.01.019 |
Abstract: | Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2',5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs. |
Rights: | © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/71413 |
Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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